tbuckley/cabot-search huggingface dataset:
Abstract 2195: A tissue atlas of oncogenic RAS mutation
Authors: Ozgun Erdogan, Christopher Counter
Journal: Cancer Research (2022)

Abstract Despite over 50 possible oncogenic RAS mutations, cancers tend to have a bias towards a specific subset unique to each cancer type. As RAS mutations could arise from selection of an ideal level (quantitative) or type (qualitative) of oncogenic signaling, we generated four conditional Kras alleles with different oncogenic mutations, G12D or Q61R, coded with native rare or common codons to induce low or high protein expression to separate these two types of signaling. These alleles were crossed into a Rosa26-CreER background and globally activated, revealing tissues sensitive to quantitative signaling regulated by the RAS biochemical activity, qualitative signaling regulated by the specific mutation, and either both or none of these two types of signaling. Bulk RNAseq analysis further revealed that each allele induced a different cellular response, with the weakest allele induce transcriptional features of a plastic state while the strongest allele had all the transcriptional hallmarks of high oncogenic signaling and a stress response. In conclusion, this approach provides a mutational atlas of tissues dependent upon quantitative signaling, qualitative signaling, or both forms of signaling for tumorigenesis, as well as tissues generally resistant to oncogenic RAS. This tissue atlas can thus serve to define how specific cancers are initiated, and in turn, how to prevent such initiation events from taking hold to lead a normal cell down the path of tumorigenesis, which has important clinical implications for early cancer detection and prevention measures. Citation Format: Ozgun Erdogan, Christopher Counter. A tissue atlas of oncogenic RAS mutation [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 2195.
Abstract 3906: Characterization of mTORC2 interactome reveals association with microtubules in glioblastoma and neuroblastoma cells
Authors: Narawit Pacharakullanon, Piriya Wongkongkathep, Fuyuhiko Tamanoi, Joseph A. Loo, Trairak Pisitkun, Naphat Chantaravisoot
Journal: Cancer Research (2022)

Abstract The Mechanistic Target of Rapamycin Complex 2 (mTORC2) is a multiprotein complex representing one of the key players in the mTOR signaling pathway. This signal transduction is essential for the regulation of various cellular activities, including proper cell growth, proliferation, differentiation, survival, cell motility, and metabolism. Aberration of the mTOR cascade can be found in several types of disorders, including cancers and neurodegenerative diseases. It has been reported to correlate with acquired aggressive characteristics promoting metastasis, drug resistance, and recurrence in cancer cells and more progressive phenotypes in other diseased cells. More specifically, mTORC2 signaling promotes actin cytoskeleton reorganization, cell motility, cell survival, and has been recently reported to be responsible for DNA damage control. Unlike mTORC1 that has been more thoroughly studied, molecular mechanisms of mTORC2 are yet to be elaborated. Therefore, characterization of the mTORC2 signaling pathway will provide further information needed for better understandings of the biology of diseases. Previously, we have identified multiple cytoskeleton regulators, including actin-binding and microtubule-associated proteins as binding partners of mTORC2 in glioblastoma cells by affinity purification-mass spectrometry (AP-MS). In this work, we provided extensive characterization of mTORC2 interactome in both neuronal and non-neuronal cells focusing on microtubule-associated proteins. Interestingly, apart from many MAP proteins found in non-neuronal cells (glioblastoma), we identified Tau isoforms and their regulatory proteins such as Tau kinases from affinity-purified mTORC2 in neuroblastoma cells. The quantitative proteomic analyses of mTORC2-interacting proteins in various cellular conditions were performed to help determine the dynamics of the mTORC2-associated microtubule network. These novel protein-protein interactions acquired from this study suggested additional mTORC2 functions in different types of brain cells, which might also be beneficial to the understandings of neurodegenerative diseases in addition to cancers. Citation Format: Narawit Pacharakullanon, Piriya Wongkongkathep, Fuyuhiko Tamanoi, Joseph A. Loo, Trairak Pisitkun, Naphat Chantaravisoot. Characterization of mTORC2 interactome reveals association with microtubules in glioblastoma and neuroblastoma cells [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 3906.
Abstract 1439: Meta-analysis of the NQO1 gene C609T polymorphism: Increased risk of colorectal cancer
Authors: Chaithanya Ganji, Raasil R. Basha, Lakkakula V.K.S. Bhaskar, Bassel F. El-Rayes
Journal: Cancer Research (2022)

Abstract Background/objective: Colorectal cancer (CRC) is aggressive and widespread (3rd among malignancies) in the United States. Recent studies suggest that metabolic pathways play an essential role in CRC. NQO1 is an enzyme that contributes to chemoprotection for CRC. Previous studies showed that the link between the NQO1 polymorphisms and CRC risk yielded conflicting results. The aim of this meta-analysis is to test the connection between NQO1 C609T polymorphisms and CRC risk. Methods: PubMed, Web of Science, and Google Scholar were used in bibliographic searches until July 17, 2021. For the NQO1 C609T analysis, a total of 18 studies (7568 CRC cases and 9003 controls) were considered. Data was gathered and subsequently calculated using the pooled odds ratio (OR) (95% confidence interval, CI). Results: The relation between NQO1 polymorphism and CRC risk (T vs. C: OR=1.17, 95% CI=1.07-1.29, p&amp;lt;0.001; TT + CT vs. CC: OR=1.19, 95% CI=1.06-1.34, p&amp;lt;0.001) was significant. Furthermore, stratified investigation based on ethnicity indicated significant association between NQO1 polymorphism and CRC risk in only Caucasian populations (T vs. C: OR=1.15, 95% CI=1.08-1.24, p&amp;lt;0.001; TT + CT vs. CC: OR=1.17, 95% CI=1.08-1.27, p&amp;lt;0.001). No proof of bias in publications was found for NQO1 polymorphism (Eggers p=0.929). Conclusion: This study indicates that the C609T polymorphism of NQO1 is linked with CRC risk in Caucasian populations. Citation Format: Chaithanya Ganji, Raasil R. Basha, Lakkakula V.K.S. Bhaskar, Bassel F. El-Rayes. Meta-analysis of the NQO1 gene C609T polymorphism: Increased risk of colorectal cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 1439.
A Child With Heart Failure and Bumpy Lesions on the Back
Authors: Balaji Arvind, Venkatakrishnan Ramakumar, Sivasubramanian Ramakrishnan
Journal: JAMA Cardiology (2022)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Cardiology HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Cardiology journal
Abstract 5279: Prognostic serum biomarkers in cancer patients with COVID-19: A systematic review
Authors: Yun-Ju Lai, Te-An Lee, Shih-Han Wang, Chia-Wei Li, Louise D. McCullough, Dhimiter Bello
Journal: Cancer Research (2022)

Abstract Purpose: COVID-19 has led to 4 million deaths worldwide since 2019. COVID-19 patients with cancers likely express biomarker changes in circulation. While many biomarker studies focused on COVID-19 diagnosis and prognosis, the panel of biomarkers used in SARS-CoV-2 infected cancer patients for COVID-19 severity and prognosis are largely unclear. Therefore, this systematic review aims to determine what biomarkers have been measured in cancer patients with COVID-19 and their prognostic utility. Methods: A systematic literature review in PubMed, Embase, and Scopus was performed on June 16th, 2021. The search keywords coronavirus, neoplasm, biomarkers, and disease progression were used to filter out 17 eligible studies, which were then carefully evaluated. Results: A total of 4,168 patients from 17 eligible articles were included in this study. Sixteen types of cancer and 60 biomarkers were identified. The majority of changed biomarkers in the cancer patients with COVID-19 compared to the healthy group and non-cancer patients with COVID-19 were biochemical and inflammatory markers. The up-regulated markers, including CRP, D-dimer, ferritin, IL-2R, IL-6, LDH, and PCT, were identified in eligible studies. Albumin and hemoglobin were significantly down-regulated in cancer patients with COVID-19. Additionally, we observed that the SARS-CoV-2 infected cancer patients with lower levels of CRP, ferritin, and LDH successfully survived from antiviral drug and immunotherapy for COVID-19 treatments. Conclusion: Several important clinical biomarkers, such as CRP, ferritin, and LDH, may serve as the prognostic markers to predict the outcomes following COVID-19 treatment and monitor the deterioration of COVID-19 in cancer patients. Citation Format: Yun-Ju Lai, Te-An Lee, Shih-Han Wang, Chia-Wei Li, Louise D. McCullough, Dhimiter Bello. Prognostic serum biomarkers in cancer patients with COVID-19: A systematic review [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 5279.
Abstract 2226: Using functional biomarkers to accurately predict advanced neoplasia in pancreatic cystic lesions
Authors: Francesco Caiazza, Andre Lourenco, Patricia Conroy, Thomas Hoffmann, Sam L. Ivry, Tyler York, Gina Zhu, Audrey Mustoe, Anthony J. O'Donoghue, Charles S. Craik, Kimberly Kirkwood
Journal: Cancer Research (2022)

Abstract Background: The accurate identification of high-grade dysplasia (HGD) or invasive cancer (advanced neoplasia, AN) in pancreatic cystic lesions (PCLs) is needed to identify PCLs that warrant surgical intervention. Cytologic evaluation of cyst fluid is widely-used but has poor sensitivity. We previously found that activity of the lysosomal serine protease tripeptidyl peptidase 1 (TPP1) is associated with mucinous PCLs that harbor AN (AUC 0.72). We aimed to identify additional functional biomarkers that would improve performance of our classifier for dysplastic grade in mucinous PCLs. Methods: We used a combination of global protease activity profiling and shotgun proteomics to identify differentiating markers between PCLs with low-grade dysplasia (LGD, n=3) and HGD (n=3). Candidate biomarkers were validated in an independent cohort of 28 clinically-annotated mucinous PCLs (HGD n=12, LGD n=16), by measuring both protein concentration (using ELISA) and enzymatic activity (using internally-quenched fluorescent substrates). We used a nested cross-validation approach to iteratively split our cohort into training and validation sets to predict HGD. Model accuracy was evaluated using area under the curve (AUC), sensitivity, specificity, and accuracy. Results: We identified 8 proteins that were highly abundant in mucinous PCLs with HGD. Among these were the inflammatory enzymes myeloperoxidase (MPO) and neutrophil elastase (ELANE), suggesting that differential activity levels could be exploited that would minimize fluid requirements and cost. Among 28 mucinous PCLs, a composite score that included both activity and mass of MPO performed the best for HGD in mucinous cysts (AUC 0.955, sensitivity 98%, specificity 93%). ELANE activity (AUC 0.76, sensitivity 69%, specificity 59%) and TPP1 activity (AUC 0.765, sensitivity 71%, specificity 74%) had modest performance. Conclusions: Our functional biomarkers accurately classified HGD among mucinous cysts. Functional biomarkers that require low sample volumes (&amp;lt;10μl) of cyst fluid have the potential to substantially improve clinical decision-making for patients with PCLs. Citation Format: Francesco Caiazza, Andre Lourenco, Patricia Conroy, Thomas Hoffmann, Sam L. Ivry, Tyler York, Gina Zhu, Audrey Mustoe, Anthony J. O'Donoghue, Charles S. Craik, Kimberly Kirkwood. Using functional biomarkers to accurately predict advanced neoplasia in pancreatic cystic lesions [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 2226.
A Review of Recent Advances and Future Developments in Fetal Phonocardiography
Authors: Radana Kahankova, Martina Mikolasova, Rene Jaros, Katerina Barnova, Martina Ladrova, Radek Martinek
Journal: IEEE Reviews in Biomedical Engineering (2022)

Fetal phonocardiography (fPCG) is receiving attention as it is a promising method for continuous fetal monitoring due to its non-invasive and passive nature. However, it suffers from the interference from various sources, overlapping the desired signal in the time and frequency domains. This paper introduces the state-of-the-art methods used for fPCG signal extraction and processing, as well as means of detection and classification of various features defining fetal health state. It also provides an extensive summary of remaining challenges, along with the practical insights and suggestions for the future research directions.
Abstract LB006: In vivo programming of myeloid cells by mRNA mediated delivery of novel Fc alpha fusion receptor activates anti-tumor immunity
Authors: Hongyun Zhao, Inna Shcherbakova, Thomas Prod’homme, Bruce McCreedy, Yuxiao Wang, Daniel Getts
Journal: Cancer Research (2022)

Abstract Immunotherapy has revolutionized cancer treatment. However, for the majority of patients with advanced solid tumors, sustained clinical benefit has yet to be achieved. Myeloid cells such as monocytes and macrophages readily accumulate in tumors, in some cases contributing up to 75% of the tumor mass. Reprogramming circulating and tumor associated myeloid cells to activate their ability to elicit anti-tumor adaptive immunity by phagocytosis, cytokine secretion and antigen presentation is an attractive approach to harness and orchestrate systemic anti-tumor immunity. It remains challenging to specifically target and activate myeloid cells in vivo. To overcome this hurdle, we have developed a novel in vivo myeloid cell engineering platform: Fc-alpha Receptor Fusion Constructs. Unlike other chimeric antigen receptors (CARs) the construct was engineered by fusing a tumor recognition scFv with the alpha chain of human Fc receptors. The stable expression and function of these receptors requires endogenously expressed Fc receptor gamma chain, a protein with limited expression to immune cells, mostly myeloid cells. Here, we present that intravenous infusion of lipid-nanoparticle (LNP) encapsulating the Fc-alpha Receptor Fusion Construct mRNA results in the uptake and expression of the construct by myeloid cells. In immunodeficient xenograft models of hepatocellular carcinoma and triple negative breast cancer, delivery of LNP mRNA encoding for GPC3 or TROP2 targeted Fc-alpha Receptor Fusion Constructs resulted in tumor killing, confirming the ability of this approach to program myeloid cells. Furthermore, in the B16 syngeneic melanoma model, treatment with the melanoma antigen GP75 targeted Fc-alpha Receptor Fusion Constructs was also associated with the initiation of broad systemic immune responses, characterized by tumoral accumulation of activated CD8+ T cells, reduced tumor associated Tregs and activation of antigen presenting cells in spleen. Together these studies highlight the potential of Fc-alpha Receptor Fusion Construct delivered directly in vivo to program myeloid cells to recognize and kill cancer. Citation Format: Hongyun Zhao, Inna Shcherbakova, Thomas Prod’homme, Bruce McCreedy, Yuxiao Wang, Daniel Getts. In vivo programming of myeloid cells by mRNA mediated delivery of novel Fc alpha fusion receptor activates anti-tumor immunity [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr LB006.
Abstract CT245: First in human CD200 activation receptor ligand and tumor lysate vaccine immunotherapy for recurrent glioblastoma in adults
Authors: Michael R. Olin, Elizabeth C. Neil, Anne Eaton, Shannon Lunn, Christopher L. Moertel
Journal: Cancer Research (2022)

Abstract Background: Immunotherapy has revolutionized clinical management of malignancies rendering cancers that previously had a dismal prognosis more manageable. Unfortunately, these therapies can cause serious immune-related adverse events, including death. In CNS cancers, currently available immunotherapies have limited to no efficacy. Our work in glioblastoma (GBM), which is considered one of the most aggressive cancers as well as being universally fatal, is focused on the CD200 immune checkpoint that modulates the immune system through the inhibitory receptor (CD200R1) and activation receptor (CD200AR). The peptide checkpoint ligand (CD200AR-L) was developed to target the CD200AR that downregulates the inhibitory PD-1/PD-L1, CTLA4 and CD200R immune checkpoints, permitting immune system activation that is less hampered by the inhibitory effects of GBM. Following a positive clinical trial in dogs that spontaneously developed high-grade gliomas, we initiated a first-in-human Phase 1 Study of the CD200 Activation Receptor Ligand (CD200AR-L) and Allogeneic Tumor Lysate Vaccine (GBM6-AD) immunotherapy for Recurrent Glioblastoma (NCT04642937). Methods: This is a single-center, first-in-human, dose-escalation Phase 1 clinical trial utilizing a 3+3 design at three dose levels; 3.75micrograms/kg, 5micrograms/kg, and 7.25micrograms/kg. Adults 18 years and old with recurrent GBM and no pre-exiting immune-related condition plus adequate performance score were eligible. Accrual started in December 2020 at dose level 1 with a second cohort having received treatment on dose level 2. CD200AR-L is administered on days 1 and 2 by suprascapular intradermal injection following the application of topical imiquimod. On day 2, a fixed dose of the allogeneic vaccine is injected intradermally at the same site. The “Induction Phase” consists of this injection series weekly for 4 weeks with monitoring for dose-limiting toxicity through Day28. The “Maintenance Phase” doses the vaccine series monthly for 2 months, then the “Booster Phase” doses every eight weeks for 24 months or until end of treatment. Patients are monitored for adverse events, including immune-mediated intracranial edema and other immune-related complications, and their neurological function is scored per NANO criteria. Correlative studies include immune monitoring (including expression of CD200R1, PD1/PD-L1, and CTLA-4) and MRI imaging assessment per iRANO criteria. Citation Format: Michael R. Olin, Elizabeth C. Neil, Anne Eaton, Shannon Lunn, Christopher L. Moertel. First in human CD200 activation receptor ligand and tumor lysate vaccine immunotherapy for recurrent glioblastoma in adults [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr CT245.
Abstract 5480: Aristolochic acid as a scaffold for antitumor drug development
Authors: Keiji Hashimoto, Rajesh Chennamshetti, Radha Bonala, Francis Johnson, Arthur P. Grollman, Viktoriya S. Sidorenko
Journal: Cancer Research (2022)

Abstract We have synthesized an analog of aristolochic acid (AA) with potent growth inhibitory activity in various human cancer cell lines and report here on mechanistic studies of this potential therapeutic. AA is a natural product and the main active principle of Aristolochia plants, a known source of antitumor agents. In 1964 due to nephrotoxicity, drug development efforts with AA were terminated following Phase I clinical trial in patients with terminal cancer of different origin. Structure activity studies of AA species allowed us to select a structural analog of AA (RJ-34) that lacks the determinants responsible for the renal toxicity and carcinogenicity of the parent compound. Building further on our experience with AA molecules, we developed a synthetic approach that affords efficient high-yield synthesis of RJ-34. Its structure and purity has been confirmed by high-performance liquid chromatography, liquid chromatography coupled with two-stage mass spectrometry and high resolution nucleic magnetic resonance. Sulforhodamine B assay revealed that RJ-34 has growth inhibitory activity in A549 and HCT-15 human cancer cell lines comparable to or stronger than that of paclitaxel or topotecan. At five nanomolar, RJ-34 inhibited DNA synthesis and cut the growth of A549 cells by 50%, leading to cell cycle arrest in G1/M and G2/S, with apparent apoptosis at concentrations greater than 200 nanomolar. Notably, protein synthesis in cultured cells, as evaluated by puromycin labelling, remained unaffected. RJ-34 was screened against the NCI-60 cell line panel - encompassing sixty human cancer cell lines from various tissues - providing clues to its mechanisms of action; namely, that RJ-34 acts through inhibition of DNA topoisomerases I and II and/or DNA intercalation. Follow-up studies using purified calf Topo I and human Topo II alpha and various plasmid substrates confirmed the role of RJ-34 as a DNA intercalator and human Topoisomerase II alpha poison. The pattern of activity of RJ-34 in the NCI-60 panel was distinct from that of AA and aristolactam - another related compound - suggesting that RJ-34 acts by mechanisms distinct from AA. In summary, RJ-34— a non-nephrotoxic analog of aristolochic acid— has a potent growth inhibitory activity in various human cancer cell lines with a mechanism of action different from the parent AA. Moving forward, pre-clinical pharmacokinetics, safety and efficacy studies are necessary to establish the potential of RJ-34 for development as an anticancer therapeutic. Citation Format: Keiji Hashimoto, Rajesh Chennamshetti, Radha Bonala, Francis Johnson, Arthur P. Grollman, Viktoriya S. Sidorenko. Aristolochic acid as a scaffold for antitumor drug development [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 5480.